U.S. patent application number 09/462757 was filed with the patent office on 2002-10-03 for nutritional composition containing methionine.
Invention is credited to HAGEMAN, ROBERT JOHAN JOSEPH.
Application Number | 20020142025 09/462757 |
Document ID | / |
Family ID | 8228562 |
Filed Date | 2002-10-03 |
United States Patent
Application |
20020142025 |
Kind Code |
A1 |
HAGEMAN, ROBERT JOHAN
JOSEPH |
October 3, 2002 |
NUTRITIONAL COMPOSITION CONTAINING METHIONINE
Abstract
An enteral food composition for clinical or dietary use,
comprises, in addition to carbohydrates and proteins or their
hydrolysates the following components or their nutritional
equivalents, per daily dosage: methionine (0.6-7 g), cysteine
(0.5-2.5 g), folic acid (0.4-8 mg), pyridoxal (vitamin B 6) (3-20
mg), zinc (18-120 mg) and at least 400 kcal energy in the form of
carbohydrates. These amounts are well above the Recommended Daily
Allowance (RDA) values. Further preferred components include
lecithin, cyanocobalamine, betaine and magnesium, as well as
transsulfuration metabolites, ATP enhancers and antioxidants.
Inventors: |
HAGEMAN, ROBERT JOHAN JOSEPH;
(WADDINXVEEN, NL) |
Correspondence
Address: |
YOUNG & THOMPSON
745 SOUTH 23RD STREET 2ND FLOOR
ARLINGTON
VA
22202
|
Family ID: |
8228562 |
Appl. No.: |
09/462757 |
Filed: |
January 31, 2000 |
PCT Filed: |
July 14, 1998 |
PCT NO: |
PCT/NL98/00408 |
Current U.S.
Class: |
424/439 ;
424/400; 424/442 |
Current CPC
Class: |
A23L 33/16 20160801;
A23V 2002/00 20130101; A61P 37/04 20180101; A23L 33/15 20160801;
A23V 2002/00 20130101; A61P 43/00 20180101; A23V 2002/00 20130101;
A61P 3/02 20180101; A61P 29/00 20180101; A23V 2002/00 20130101;
A23L 33/175 20160801; A23V 2250/1626 20130101; A23V 2250/5114
20130101; A23V 2250/188 20130101; A23V 2250/1642 20130101; A23V
2250/702 20130101; A23V 2250/06 20130101; A23V 2250/161 20130101;
A23V 2250/7104 20130101; A23V 2250/704 20130101; A23V 2250/0616
20130101; A23V 2250/705 20130101; A23V 2250/065 20130101; A23V
2250/18 20130101; A23V 2250/1868 20130101; A23V 2250/1944 20130101;
A23V 2250/0632 20130101; A23V 2250/156 20130101; A23V 2250/5486
20130101; A23V 2250/714 20130101; A23V 2250/70 20130101; A23V
2250/708 20130101; A23V 2250/1882 20130101; A23V 2250/54252
20130101; A23V 2250/54246 20130101; A23V 2250/70 20130101; A23V
2250/1612 20130101; A23V 2250/0642 20130101; A23V 2250/0606
20130101; A23V 2250/30 20130101; A23V 2250/1588 20130101; A23V
2002/00 20130101; A23V 2002/00 20130101 |
Class at
Publication: |
424/439 ;
424/442; 424/400 |
International
Class: |
A61K 047/00; A61K
009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 14, 1997 |
EP |
97202206.5 |
Claims
1. Food composition which is a complete enteral food for clinical
or dietary use, containing per daily dosage: (a) an energy content
of 5024-10467 kJ (1200-2500 kcal), supplied by carbohydrates, fats
and proteinaceous material, the carbohydrates accounting for at
least 25% of the energy content and the proteinaceous material
being present in an amount of at least 20 g, at least 50% of the
proteinaceous material being present as proteins or peptides, and
(b) the following components or their nutritional equivalent: 0.6-7
g of methionine and cysteine taken together, 0.4-8 mg of folic
acid, 3.2-20 mg of pyridoxal (vitamin B.sub.6) and 24-120 mg of
zinc.
2. Food composition according to claim 1, wherein a least 30 energy
% is in the form of fats, further containing at least 70 g of
proteinaceous material per daily dosage, at least 50% thereof being
in the form of proteins, and at least 1 g of methionine and at
least 0.5 g of cysteine per daily dosage, the composition
optionally being in the form of multiple dosage units.
3. Food composition which is an enteral food supplement for
clinical or dietary use to be used in addition to a non-medicinal
food, containing per daily dosage, (a) an energy content from 1675
up to less than 6280 kJ (from 400 to less than 1500 kcal), supplied
by at least carbohydrates and proteinaceous material, soluble
digestible carbohydrates being present in amount of at least 100 g
and the proteinaceous material being present in amount of at least
20 g, at least 50% of the proteinaceous material being present as
proteins or peptides, and (b) the following components or their
nutritional equivalents, 0.6-7 g of methionine and cysteine, 0.4-8
mg of folic acid, 3.2-20 mg of pyridoxal (vitamin B.sub.6) and
24-120 mg of zinc.
4. Food composition according to claim 3, containing 1675-4187 kJ
(400-1000 kcal) per daily dosage.
5. Food composition according to any one of claims 1-4, wherein at
least one of said components is comprised in the following amounts,
per daily dosage; methionine and cysteine (1.6-4-g), methionine
according for at least half of said amount, folic acid (0.6-3 mg),
pyridoxal (4-12 mg), zinc (30-100 mg), and at least 800 kcal in the
form of carbohydrates.
6. Food composition according to any one of claims 1-5, further
containing at least 0.8 g, preferably 1.6-1.2 g of phospholipids,
per daily dosage.
7. Food composition according to any one of claims 1-6, further
comprising at least one of the following components or their
nutritional equivalents, per daily dosage: cyanocobalamine (vitamin
B.sub.12) (2-20 .mu.g, preferably 3.6-10 .mu.g), magnesium (200-700
mg, preferably 300-500 mg) and betaine and/or choline (0.3-6,
preferably 0.6-3 g); (b) creatine (0.5-40, preferably 2-25 g),
carnitine (0.2-4, preferably 0.4-2 g), taurine (15-150, preferably
30-80 mg), and nucleotides (0.1-4, preferably 0.4-2 g); (c)
pyruvate (2-20, preferably 4-8 g), riboflavin (vitamin B.sub.2)
(2-10 mg, preferably 2.5-6 mg), niacin (25-170 mg, preferably 35-85
mg), thiamine (2-10 mg, preferably 3-6 mg), D-biotin (50-500,
preferably 100-300 .mu.g), and thioctic acid (5-200, preferably
10-50 mg); (d) manganese (9-60 mg, preferably 10-30 mg), copper
(3-14 mg, preferably 4-10 mg), selenium (80-300 .mu.g, preferably
100-150 .mu.g), ascorbic acid (vitamin C) (100-900 mg, preferably
150-300 mg), and tocopherol (vitamin E) (15-180 mg, preferably
20-40 mg); (e) serine (3-12 g) and optionally arginine or ornithine
(2-10 g), glutamine (5-30 g), the composition containing less than
5.2 g of threonine per 100 g of proteinaceous material; and
preferably at least one component from each of the groups
(a-e).
8. Food composition according to any one of claim 1-7, which is in
a liquid form having an energy density of at least 4.2 kJ, up to
10.5 kJ/ml (1-2.5 kcal/ml).
9. Food composition according to any one of claims 1-8, which is in
a powder form to be reconstituted with water.
10. Process of producing a food composition according to any one of
claims 1-9, which comprises preparing a premix of at least said
methionine/cysteine, folic acid, pyridoxal and zinc, optionally
with carbohydrate as a carrier.
11. Use of a composition according to any one of claim 1-9 for
preparing a medicinal composition for the treatment of prophylaxis
of increased plasma level of homocysteine, cardiovascular diseases,
imparted immune function, inflammatory diseases, autoimmune
diseases, arthritis, wound healing after surgery, decubitus,
cancer, premature ageing, allergic conditions or neural disorders.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a module of nutritional
components which supports total methionine metabolism in man, for
use in a universal medicinal food. The invention also relates to
food products containing this module and to a method of producing
food products by using selected amounts of the module.
BACKGROUND
[0002] Methionine is metabolised in man via a multi-step pathway,
the transsulfuration pathway. Several intermediate products are
formed in this pathway, which play a dominant role in other
biochemical pathways as well. For example, the reaction product
S-adenosyl methionine is extensively used in many methylation
reactions; homocysteine is the main methyl acceptor in folate
metabolism and also the conversion of betaine to dimethylglycine
(via methylation of homocysteine) strongly influences folate
metabolism.
[0003] Another intermediate in the transsulfuration pathway is
cystathionine generated by reaction between homocysteine and
serine, that may split into cysteine and 2-oxy-butyrate. The latter
is involved in the metabolism of several other compounds (e.g.
threonine). Cysteine is metabolised to various useful products such
as taurine and sulphates. It is also an important precursor for
glutathione in the liver and some other tissues. Glutathione that
is produced in the liver has to be transported to cell compartments
in some peripheral organs in order to exhibit its activity.
Intracellular glutathione levels are in turn strongly influenced by
the presence of reducing equivalents and amino acids in the
cell.
[0004] Herein we define total methionine metabolism as those
biochemical pathways which occur in mammals and in which
metabolites of the methionine transsulfuration pathway (methionine,
S-adenosyl methionine, S-adenosyl homocysteine, homocysteine,
cystathionine and cysteine) and main metabolites thereof (taurine
and glutathione) are involved (see scheme below).
[0005] Many diseases in man have been associated with impaired
functioning of parts of total methionine metabolism. Lack of the
body capacity for methylation (by shortages of available S-adenosyl
methionine) has been related to diseases like cancer, improper
wound healing, diabetes, neurological diseases like Alzheimer or
Parkinson' disease (WO 96/33703). Shortages of folate have been
associated with neural defects and several other problems.
[0006] Dysfunction of methionine metabolism may also lead to
increased homocysteine plasma levels, which are associated with
cardiovascular problems. Cysteine deficiencies may lead to low
taurine levels, low sulphation capacity and low intracellular
glutathione levels. Shortages of cysteine have been associated with
diseases like diabetes, cardiovascular disease, cancer, rheumatoid
arthritis, etc.
[0007] Glutathione can play many important roles in the cell. A
substantial part of glutathione must be in the reduced form (having
a specific redox potential) in order to allow it to be active.
Deficiencies of glutathione have been associated with all kinds of
radical-mediated diseases, such as chronic inflammations,
rheumatoid arthritis, with the occurrence of cancer and impaired
immune functions against infection.
[0008] EP-A-532369 (Bissbort) describes the pharmaceutical use of
L-methionine for enhancing the methylation capacity in man, e.g.
for improving the immune response, combating viral infections and
increasing creatine production. Methionine may be combined with
folic acid, pyridoxine (vitamin B.sub.6), cyanocobalamine (vitamin
B.sub.12) and magnesium. A daily dose comprises 1.5-5 g (3 g) of
L-methionine, 250-2500 mg (600 mg) of magnesium chloride, 30-120 mg
(100 mg) of magnesium carbonate, 0.6-20 mg (8 mg) of folic acid,
1.5-25 mg (10 mg) of vitamin B.sub.6 and 15-25 .mu.g (20 .mu.g) of
vitamin B.sub.12.
[0009] WO 93/15738 (Waldthaler) discloses medicaments containing
thymine or its equivalents in combination with methionine,
pyridoxine and/or cyanocobalamine and optionally penicillin G for
the treatment of disorders in the folate metabolism.
[0010] WO 96/02252 and WO 96/33727 (Knoll) disclose the use of
S-adenosyl-L-methionine for the treatment of damage caused by
temporary and permanent local ischaemias, respectively.
[0011] EP-A-347864 (Strydom) discloses an anti-atherogenic agent
which lowers the plasma level of free sulphydryl groups of
homocysteine and cysteine and which can contain oxidising agents
and folic acid, pyridoxine (vitamin B.sub.6), cyanocobalamine
(vitamin B.sub.12) and choline or betaine.
[0012] Likewise, EP-A-595005 and EP-A-595006 (Vesta) teach the use,
for adults and infants respectively, of specific ratios of folic
acid, pyridoxine and cyanocobalamine for suppressing high
homocysteine and methionine levels in plasma, which are the cause
of metabolic disturbances. According to the latter document,
pyridoxine should at least partly be present in its accessible
pyridoxal form. Riboflavin (vitamin B.sub.2), ascorbic acid
(vitamin C), tocopherol (vitamin E), zinc and selenium may also be
present.
[0013] EP-A-705542 discloses a complete dietary composition for
adolescents and especially for children of 1 to 6 years having
diseases such as intestinal disorders. The composition contains
50-65 (63) energy % of carbohydrates, 20-35 (25) en. % of fats and
10-20 (12) en. % of free amino acids with a specific amino acid
content.
[0014] A multivitamin preparation supporting the immune system is
disclosed in GB-A-2,292,522. It contains an amino acid blend,
vitamins C, E, A, D and B complex, minerals and trace elements.
Important amino acids are: methionine (90 mg), valine, leucine,
threonine (70 mg), phenylalanine, lysine, isoleucine and
tryptophane. Levels of B complex vitamins may be: B1 (50 mg), B2
(100 mg), B6 (100 mg), pantothenic acid (300 mg), nicotinamide (50
mg), B12 (2.5 .mu.g), folic acid (150 .mu.g) and biotin (50 .mu.g).
The preparation does not contain carbohydrates or full proteins. No
recommended dosages are given.
[0015] U.S. Pat. No. 5,215,750 discloses a composition for inducing
weight loss, containing glutamine as the major component, and
further a broad range of vitamins and minerals, without further
amino acids, proteins, carbohydrates or fats.
[0016] Despite these proposals, the diseases referred to above are
still very common and therefore there exists a need for nutritional
products that may support prevention and treatment of these
diseases.
[0017] Many persons suffer from deficiencies in essential amino
acids, such as methionine, essential fatty acids, vitamins,
minerals, trace elements or other food components, as a result of
bad eating habits, disorders in nutrient absorption, or increased
nutrient demands. A minority of patients suffer from metabolic
disorders in the transsulfuration pathway; some enzymes have low
activity or do not function at all. Thus there is a need for a
nutritional product which supports total methionine metabolism and
at the same time compensates for the shortages in nutrients that
may occur in patients in need of support of methionine
metabolism.
[0018] Several intermediates of total methionine metabolism can be
quite reactive in the human body, and the reactive forms (reduced
homocysteine, cysteine, glutathione) are not easily transported
over the cell membranes. It is therefore important to support the
methionine metabolism in such a way that no undesired side effects
occur and at the same time intracellular levels of useful
intermediates are maintained, even in the diseased state.
[0019] The reactive species are also easily oxidised in aqueous
solution, and it is therefore an object of the invention to provide
a nutritional composition with a sufficient shelf stability. Some
nutritional components that play an important part in the
methionine metabolism have bad organoleptic properties. It is
therefore an object of the invention to provide a nutritional
product that is well acceptable to the consumer.
[0020] Many attempts have been made up to now to find solutions to
these problems. All these prior attempts have concentrated on a
part of the total methionine metabolism, relying on an adequate
functioning of the rest of the biochemical pathways of total
methionine metabolism in man to maintain homeostasis and meet
physiological demands. For supporting these parts, either too low
or too high amounts were suggested.
[0021] It has now been found that it is essential to provide
patients with a combination of components that play a key role in
the various parts of total methionine metabolism as depicted in the
scheme below, and to provide them in an excess amount in the form
of a (medicated) nutritional composition in order to give
nutritional support to the maximum number of patients. In this
context "nutritional" means at least partly satisfying the energy
needs in addition to having a medicinal effect.
[0022] It has furthermore been found to be advantageous to
administer other components that play a role in total methionine
metabolism as well. Such other components comprise end products and
intermediates for giving a more rapid response and for meeting
requirements for those patients that have deficiencies in one or
more key enzymes that are involved in total methionine
metabolism.
[0023] The invention pertains to an enteral food composition
containing at least digestible, in particular glucose or
.alpha.-glucan, carbohydrates and proteins or protein hydrolysates
and a combination of active components as defined in the appending
claims. The amounts of the components of the food composition of
the invention are related to the Recommended Daily Allowance (RDA)
and other recommendations as used in standard nutrition literature.
The reference values based on these RDA values for components that
can be used according to the invention, together with the preferred
ranges of total intake per day, are given in table 1 below. The
reference are based on healthy adults having a body weight of 70
kg. For patients of different condition and different body weight,
the levels should be adapted accordingly. It is to be understood
that on average the energy intake per day should be about 2000
kcal.
[0024] Where reference is made to nutritional equivalents of the
components, this includes any compound which under physiological
conditions yields the component in question in equimolar
amounts.
1TABLE 1 Reference values and preferred levels according to the
invention reference general preferred component mg/day mg/day
mg/day methionine/cysteine* 1100 600-7,000 1,600-4,000 folic acid
0.2 0.4-8 0.6-3 pyridoxal 2.0 3.2-20 4-12 cyanocobalamine 0.0015
0.002-0.02 0.0036-0.01 magnesium 300 200-700 300-500 riboflavin 1.5
2-10 2.5-6 niacin 17 NE 25-170 35-85 thiamine 1.5 2-10 3-6 zinc 12
24-120 24-100 manganese 6 9-60 10-30 copper 2.0 3-14 4-10 selenium
0.07 0.08-0.3 0.1-0.15 ascorbic acid 65 100-900 150-300 tocopherol
10 a-TE 15-180 20-40 *as methionine, S-adenosyl methionine,
S-adenosyl homocysteine, homocysteine, cystathionine, cysteine,
cystine, glutathione or other equivalents (see text).
[0025] Nutritional equivalents of amino acids include di- or
oligopeptides incorporating said amino acid, esters, amides and
salts of the amino acids, as well as S-substituted derivatives in
the case of sulphur-containing amino acids, including methionine,
S-acetylmethionine, S-acetylhomocysteine, homocysteine,
cystathionine, cysteine, cystine, glutathione and other dimers and
trimers derived from these. The sulphur amino acids other than
methionine and cysteine can be used instead as a substitute of
methionine and cysteine, although the latter two are preferred.
Suitable examples of a cysteine equivalent are N-acetylcysteine and
bisglycylcystine. Proteins may also be used as amino acid sources,
provided that the desired amino acids become readily available by
digestion. Methionine-rich proteins include e.g. casein, caseinates
and casein hydrolysates. Cysteine-rich proteins include dairy whey
proteins and specific proteins thereof such as lactalbumin, as well
as blood proteins, egg proteins and other proteins which are rich
in sulphur-containing amino acids and hydrolysates thereof. Thus
the required level of sulphur-containing amino acids can be
attained e.g. by combining casein with cysteine, N-acetylcysteine
or a cysteine-rich peptide or by combining whey protein with
methionine or a methionine-rich peptide. Preferably, proteins that
are rich in essential amino acids are also present.
[0026] Nutritional equivalents of pyridoxal (vitamin B.sub.6)
include pyridoxal phosphate, pyridoxine and pyridoxamine and salts
and the like. Nutritional equivalents of niacin (nicotinic acid)
include niacinamide (nicotinamide) and tryptophan. The preferred
equivalent of thiamine (vitamin B.sub.1) is its hydrochloride.
[0027] Among the components given in table 1, methionine/cysteine,
folic acid, pyridoxal and zinc should be present in addition to the
energy content. These components, including the carbohydrate
content, were found to be essential as primary support of the
transsulfuration pathway. At least half of the methionine/cysteine
content should consist of methionine or a methionine equivalent. A
second group of important components includes magnesium,
cyanocobalamine and betaine/choline. Preferably, at least one of
these is also present in the food compositions of the invention.
Magnesium is preferred, but at around or slightly above the
reference level only. Suitable magnesium salts include magnesium
hydrogen phosphate and magnesium sulphate. A third group comprises
transsulfuration products, including creatine, carnitine, taurine
and nucleotides. At least one of these is also advantageously
present in the food composition. A fourth group of components is
important as they stimulate carbohydrate metabolism and produce ATP
and reducing equivalents. At least one member of this group which
includes pyruvate, thiamine, riboflavin, niacin, biotin and
thioctic acid, is preferably present as well. A final group
comprises ascorbic acid, tocopherol, selenium, copper and
manganese. The incorporation of ascorbic acid and/or tocopherols is
preferred for ensuring that reduced glutathione is spared from
excessive attack by radicals or oxidation processes. Ascorbic acid
may be present as a nutritionally acceptable salt, and tocopherol
as any one or a combination of isomers, e.g. tocopherol. Other
antioxidants or radical scavengers like carotenoids, flavonoids,
uric acid etc. may be included as well. Similarly, the trace
elements Cu, Se and Mn are preferably included, as they are
essential for key enzymes that neutralise oxygen-containing
radicals. The preferred range for Cu and Mn is 2-5 times the
reference value; for selenium it is about 1.5 times the reference
value.
[0028] The other components of table 1 are also preferred
individually, i.e. the selection of a single component, e.g.
riboflavin or manganese, forms a distinct embodiment of the
invention. Components for which a reference level is not given in
table 1, are also advantageously incorporated in the composition of
the invention. The methyl donor betaine (N,N,N-trimethylglycine, as
its inner salt or its hydrochloride) and/or one of its precursors
choline and phosphatidylcholines (occurring in certain lecithins)
is preferably included in order to stimulate an independent pathway
for the conversion of homocysteine to methionine. For reasons of
taste, betaine itself is preferred over its equivalents.
[0029] Creatine (N-guanidyl-N-methylglycine) can be incorporated as
such, as its phosphate or as an analogue such as guanidine
derivatives, in the levels indicated, with a preferred level of
around 10 g/day. L-Carnitine can be given as such (inner salt) or
as its hydrochloride. Creatine and/or carnitine are especially
preferred for patients having a poor blood circulation, or
suffering from local ischaemic conditions. D-Biotin (generally
preferred) and taurine can be included as such, taurine especially
for infants and neurological patients. Nucleotides can also be
advantageously included, preferably as yeast extract in an amount
of about 0.1-4 g/day, for example in products for the treatment of
inflammatory diseases of the gut.
[0030] Pyruvate is another component that can contribute to the ATP
production and can protect glutathione as a radical scavenger. The
preferred level is from 2 to 20 g/day, especially 4-8 g/day.
Pyruvate can be incorporated e.g. as free acid or as its Ca, Na or
K salt. DL-Thioctic acid (lipoic acid) is also preferred for
increasing the level of ATP produced. Niacin, riboflavin and
thiamine also stimulate carbohydrate metabolism and produce ATP and
reducing equivalents.
[0031] Furthermore, usual components can be incorporated at or
above the recommended amounts, especially
calciferol/cholecalciferol/dihydrocalcife- rol (vitamin D) and
phosphate. The composition should comprise sufficient levels of
essential amino acids such as lysine in accessible form, so that
the total intake corresponds at least to the reference levels. Some
non-essential amino acids are also preferably included in the
composition of the invention. These comprise especially serine, and
furthermore glutamine and arginine/ornithine at the indicated
levels as such (L-form) or as easily degradable peptides or
proteins. Threonine is preferably not present in important amounts,
i.e. preferably lower than 5.2 g per 6.25 g of nitrogen (<5.2 g
per 100 g of proteinaceous material). Proteins which are low in
threonine include acid whey.
[0032] The compositions contain carbohydrates, preferably proteins
and preferably fats. In a complete food, the carbohydrates should
constitute at least 25% of the required energy content, i.e. at
least 400 kcal/day, up to 1500 kcal/day. The carbohydrates can
comprise mono-, di-, oligo- and polysaccharides, such as glucose,
fructose, maltose, sucrose, fructo-, galacto- and especially
gluco-oligosaccharides, starch, starch hydrolysates and starch
fractions and the like. The carbohydrate composition can be adapted
to the type of patients. For diabetes patients, slowly degrading
carbohydrates like fructose polymers may be present together with a
relatively large amount of high molecular weight maltodextrins.
Generally, the carbohydrate compositions is low in lactose. The
compositions may furthermore contain dietary fibres such a
non-digestible carbohydrates. The proteins may be those described
above as sources for the desired amino acids, including milk
proteins, egg proteins, blood proteins. For reasons of taste, it is
preferred that at least half of the total proteinaceous material
(proteins, hydrolysates and amino acids) is in the form of proteins
or peptides, especially in the form of intact proteins.
[0033] The fats may comprise normal fats C.sub.12-C.sub.18 derived
from saturated and especially unsaturated fatty acids. The fats may
include medium chain triglycerides derived from C.sub.8 and
C.sub.10 fatty acids (e.g. accounting for 5-40 wt. % of the fats),
and preferably polyunsaturated long-chain (.gtoreq.C.sub.18) fats
(PUFA's) derived from .omega.-3 fatty acids such as
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
(preferably at least 3 wt. %, in particular 5-15 wt. % of the
fats). The .omega.-3/.omega.-6 ratio is preferably from 0.3 to 3.
For complete foods, the fat content is preferably more than 30% of
the total energy content, especially more than 35 en. %, up to 45
en. %. The fats should contain phospholipids such as lecithin or an
equivalent thereof at a level of 1-20 wt. % of the fat content, or
0.3-10 en. %, preferably 0.6-5 en. % of the composition. The
phospholipids can be partly (i.e. the amount above 5 wt. % of the
fat content) substituted by equivalents such as choline or
betaine.
[0034] The food composition can have the form of a complete food,
i.e. all the nutritional needs of the user. As such it will usually
containing 1200-2500 kcal per daily dosage, apart from higher or
lower amounts in exceptional cases. The daily dosage amounts are
given with respect to a daily energy supply of 2000 kcal, but can
be adapted accordingly. The complete food can be liquid, wherein
the daily dosage is contained in e.g. 2000 ml; more diluted or,
especially, more concentrated liquids can also be used. The
composition can also be in solid form for reconstitution with
water. The complete food can be in the form of multiple dosage
units, e.g. from 3 to 10 per day.
[0035] The food composition of the invention can also be a food
supplement to be used in addition to a non-medicinal food,
containing less than 1500 kcal, in particular 400-1000 kcal, per
daily dosage. Such food supplement preferably also contains at
least part of the carbohydrate and protein supply, so that the need
of essential amino acids and serine is met with the supplement. A
very useful supplement contains the essential components at the
levels indicated above (methionine/cysteine, folic acid, vitamin
B.sub.6, zinc and optionally magnesium, vitamin B.sub.12,
betaine/choline, serine and/or tryptophan with a suitable carrier
such as maltodextrin in dry form, e.g. in sachets of 10 g. The
content of the sachet may be added to regular food or to food
components so as to provide the daily doses according to the
invention.
[0036] The invention also relates to a process of producing a food
composition, which comprises preparing a premix of at least said
methionine/cysteine, folic acid, pyridoxal and zinc, optionally
with a relatively small amount of maltodextrin or other
carbohydrate as a carrier. Further components are then added to
said premix, for example by subsequent addition of other premixes.
The use of premixes may simplify and/or standardise the preparation
of especially adapted food compositions directed at specific needs.
Also from an economical point of view, and from the point of view
of minimising mistakes during processing, it is therefore
advantageous to produce a single premix of components that can be
used in the manufacture of several types of enteral clinical
nutrition.
[0037] As the module of components supports total methionine
metabolism, it has universal benefit in many types of clinical
nutrition. The universal character of the food composition of the
invention obviates the need to await the result of some types of
clinical analyses of patients. The module can be added in response
to specific nutritional demands. The compositions can be adapted
for clinical nutrition, infant formulae, nutrition for persons at
risk for specific diseases, enteral nutrition during pregnancy, and
dietetic supplements. The food compositions can be used for the
treatment or prophylaxis of increased plasma level of homocysteine,
cardiovascular diseases, imparted immune function, inflammatory
diseases, autoimmune diseases such as arthritis, wound healing
after surgery, decubitus, cancer, premature ageing, allergic
conditions, neural disorders,
EXAMPLE 1
[0038] Three standard mixtures of active components were prepared
by dry mixing the amounts as indicated in tables 2 and 3 and
optionally table 4.
2TABLE 2 Ingredient mixture A for support of total methionine
metabolism amount per 100 kg of premix A maltodextrins 74 kg
L-methionine 8 kg N-acetylcysteine 2 kg folic acid 6 g pyridoxine
60 g zinc sulphate 500 g (=200 g Zn) cyanocobalamine on carrier 30
g (=30 mg B12) magnesium phosphate 3 aq. 14 kg (=2 kg Mg)
[0039]
3TABLE 3 Ingredient mixture B for support of total methionine
metabolism amount per 100 kg of premix B maltodextrins 89 kg
betaine 10 kg nicotinamide 510 g NE riboflavine 30 g thiamine.HCl
30 g manganese sulphate 4 aq. 320 g (=80 g Mn) cupric sulphate 5
aq. 150 g (=40 g Cu)
[0040]
4TABLE 4 Ingredient mixture C for support of total methionine
metabolism amount per 200 kg of premix C maltodextrins 40 kg
creatine 100 kg L-carnitine 12 kg taurine 400 g ascorbic acid 2.0
kg alfa-tocopherol 200 g TE soy lecithin 5 kg L-biotin on a carrier
200 g (=2 g L-biotine) sodium selenate on a carrier 370 g (=1 g Se)
L-serine 30 kg L-tryptophan 10 kg
EXAMPLE 2
[0041] Complete enteral tube feeding in dry form.
[0042] The ingredients as listed below are dissolved in 2000 l
water.
5 Composition of aqueous phase of complete enteral nutrition amount
per 2000 1 caseinates (50% Na, 50% Ca) 60 kg protein isolate from
acid whey 40 kg ingredient mixture A 10 kg ingredient mixture B 10
kg ingredient mixture C 20 kg maltodextrins 280 kg L-arginine 6 kg
wheat hydrolysate 30 kg fibres (inulin/soy: 2/1) 16 kg calcium
phosphate 0.6 kg magnesium phosphate 0.4 kg sodium chloride 0.9 kg
potassium citrate 5 kg lecithin 4.4 kg standard trace element
premix 250 g (which comprises 20 g Fe, 3 g Cu, 100 mg Mo, 2 mg F,
20 g Zn, 6 g Mn, 66 mg Cr, 200 mg I, 40 mg Co and 10 g Se) standard
vitamin premix 20 g (which comprises pantothenic acid 8 g, thiamine
2 g, riboflavin 2.2 g, niacin 4.2 g NE, vitamin B6 2.6 g, biotine
200 mg and folic acid 260 mg) meso-inositol 50 g yeast extract 1
kg
[0043] After dissolving the ingredients, the aqueous phase is set
on pH 6.5-8 and stirred until use. In a separate tank the fat blend
as exemplified below is prepared by methods known in the art
(pumping the appropriate amounts in the tank at elevated
temperature (e.g. 50.degree. C.) and the fat-soluble vitamins (A,
D2, K and E) are added and the mixture stirred until use).
6 Fat blend composition; amounts in kg per 100 kg sunflower oil
(high oleic acid) 28 sunflower oil 12 rapeseed oil 52 fish oil
(high DHA) 2 MCT oil 6 vitamin premix vitamin A 1.4 g vitamin D2 10
mg vitamin K 100 mg vitamin E 100 g
[0044] The aqueous phase is pumped to a homogeniser arranged before
a pasteuriser and static mixer. The fat phase is carefully dosed to
the aqueous phase before it reaches the mixer, in a ratio of 1 part
fat phase to 16 parts of the pasteurised aqueous phase. Immediately
thereafter the mixture is homogenised and pumped to a heat
exchanger where the water is evaporated and the resulting product
spray-dried and packed in cans.
EXAMPLE 3
[0045] A nutritional supplement for the elderly
[0046] In 2000 liter tap water are dissolved:
7 70 kg skimmed milk powder (delactosed) 64 kg saccharose 5 kg soy
lecithin 10 kg algae oil 10 kg canola oil
[0047] This mixture is pasteurised and fermented.
[0048] Then are added:
8 20 kg mixture A (of example 1) 6 kg pectine 200 kg glucose syrup
(Glucidex) 2 kg choline chloride 2.4 kg calcium chloride 2.4 kg
potassium phosphate 1.5 kg potassium lactate 260 g sodium ascorbate
2.0 kg potassium citrate 40 kg fruit concentrate 1 kg
flavourings
[0049] The mixture is set on pH 3.8-4.4, pasteurised and filled
aseptically into 500 ml cartons.
EXAMPLE 4
[0050] Supplement for persons with volume restrictions (infants,
persons suffeying from illness, cancer or neuropathic diseases)
[0051] Packed in 1 liter cartons.
9 Amount per 100 ml Energy 150 kcal Protein (casein/whey 80/20) 8.2
g (=0.3 g Met + Cys) Tryptophan 0.1 g Carbohydrates 16.5 g
Maltodextrin 10.5 g Sucrose 6.0 g Fats 5.5 g Saturated 1.3 g
Mono-unsaturated 1.8 g PUFA's 2.1 g from vegetable oils, lecithin +
DHA/EPA source (0.1 g) Fibre (inulin/soy 1:1) 0.4 g Sodium 60-100
mg Potassium 140-210 mg Chloride 80-150 mg Calcium 230 mg
Phosphorus 150 mg Magnesium 35 mg Iron 2.0 mg Zinc 6.0 mg Copper
0.6 mg Manganese 2.0 mg Fluorine 0.2 mg Molybdene 10 .mu.g Selenium
10 .mu.g Chromium 6.6 .mu.g Iodine 20 .mu.g Vitamin A 166 .mu.g RE
Vitamin D 2.0 .mu.g .alpha.-Tocopherol 4.9 mg Vitamin K 8.0 .mu.g
Thiamine 0.4 mg Riboflavin 0.4 mg Niacin 6 mg NE Pantothenic acid
0.8 mg Vitamin B.sub.6 1.0 mg Folic acid 100 .mu.g Vitamin B.sub.12
0.3 .mu.g Biotin 20 .mu.g Vitamin C 13 mg Betaine 20 mg Taurine 4
mg
EXAMPLE 5
[0052] Food supplement
[0053] The mixture of table 2 (example 1) was filled in sachets of
10 g each. 1
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